Publications by authors named "Kenji Watanabe"

1,180 Publications

  • Page 1 of 1

Evidence of Orbital Ferromagnetism in Twisted Bilayer Graphene Aligned to Hexagonal Boron Nitride.

Nano Lett 2021 May 10. Epub 2021 May 10.

Stanford Institute for Materials and Energy Science, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, California 94025, United States.

We have previously reported ferromagnetism evinced by a large hysteretic anomalous Hall effect in twisted bilayer graphene (tBLG). Subsequent measurements of a quantized Hall resistance and small longitudinal resistance confirmed that this magnetic state is a Chern insulator. Here, we report that when tilting the sample in an external magnetic field, the ferromagnetism is highly anisotropic. Because spin-orbit coupling is weak in graphene, such anisotropy is unlikely to come from spin but rather favors theories in which the ferromagnetism is orbital. We know of no other case in which ferromagnetism has a purely orbital origin. For an applied in-plane field larger than 5 T, the out-of-plane magnetization is destroyed, suggesting a transition to a new phase.
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http://dx.doi.org/10.1021/acs.nanolett.1c00696DOI Listing
May 2021

Evidence for Moiré Trions in Twisted MoSe Homobilayers.

Nano Lett 2021 May 10. Epub 2021 May 10.

State Key Laboratory of Low-Dimensional Quantum Physics and Department of Physics, Tsinghua University, Beijing 100084, P.R. China.

Moiré superlattices of van der Waals structures offer a powerful platform for engineering band structure and quantum states. For instance, Moiré superlattices in magic-angle twisted bilayer graphene, ABC trilayer graphene have been shown to harbor correlated insulating and superconducting states, while in transition metal dichalcogenide (TMD) twisted bilayers, Moiré excitons have been identified. Here we show that the effects of a Moiré superlattice on the band structure are general: In TMD twisted bilayers, excitons and exciton complexes can be trapped in the superlattice in a manner analogous to ultracold bosonic or Fermionic atoms in optical lattices. Using twisted MoSe homobilayers as a model system, we present evidence for Moiré trions. Our results thus open possibilities for designer van der Waals structures hosting arrays of Fermionic or bosonic quasiparticles, which can be used to realize tunable many-body states crucial for quantum simulation and quantum information processing.
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http://dx.doi.org/10.1021/acs.nanolett.1c01207DOI Listing
May 2021

Programmable Bloch polaritons in graphene.

Sci Adv 2021 May 7;7(19). Epub 2021 May 7.

Department of Physics, Columbia University, New York, NY 10027, USA.

Efficient control of photons is enabled by hybridizing light with matter. The resulting light-matter quasi-particles can be readily programmed by manipulating either their photonic or matter constituents. Here, we hybridized infrared photons with graphene Dirac electrons to form surface plasmon polaritons (SPPs) and uncovered a previously unexplored means to control SPPs in structures with periodically modulated carrier density. In these periodic structures, common SPPs with continuous dispersion are transformed into Bloch polaritons with attendant discrete bands separated by bandgaps. We explored directional Bloch polaritons and steered their propagation by dialing the proper gate voltage. Fourier analysis of the near-field images corroborates that this on-demand nano-optics functionality is rooted in the polaritonic band structure. Our programmable polaritonic platform paves the way for the much-sought benefits of on-the-chip photonic circuits.
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http://dx.doi.org/10.1126/sciadv.abe8087DOI Listing
May 2021

Bosonic condensation of exciton-polaritons in an atomically thin crystal.

Nat Mater 2021 May 6. Epub 2021 May 6.

Technische Physik and Würzburg-Dresden Cluster of Excellence ct.qmat, Universität Würzburg, Würzburg, Germany.

The emergence of two-dimensional crystals has revolutionized modern solid-state physics. From a fundamental point of view, the enhancement of charge carrier correlations has sparked much research activity in the transport and quantum optics communities. One of the most intriguing effects, in this regard, is the bosonic condensation and spontaneous coherence of many-particle complexes. Here we find compelling evidence of bosonic condensation of exciton-polaritons emerging from an atomically thin crystal of MoSe embedded in a dielectric microcavity under optical pumping at cryogenic temperatures. The formation of the condensate manifests itself in a sudden increase of luminescence intensity in a threshold-like manner, and a notable spin-polarizability in an externally applied magnetic field. Spatial coherence is mapped out via highly resolved real-space interferometry, revealing a spatially extended condensate. Our device represents a decisive step towards the implementation of coherent light-sources based on atomically thin crystals, as well as non-linear, valleytronic coherent devices.
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http://dx.doi.org/10.1038/s41563-021-01000-8DOI Listing
May 2021

Single-spin resonance in a van der Waals embedded paramagnetic defect.

Nat Mater 2021 May 6. Epub 2021 May 6.

3. Physikalisches Institut, Universität Stuttgart, Stuttgart, Germany.

A plethora of single-photon emitters have been identified in the atomic layers of two-dimensional van der Waals materials. Here, we report on a set of isolated optical emitters embedded in hexagonal boron nitride that exhibit optically detected magnetic resonance. The defect spins show an isotropic g-factor of ~2 and zero-field splitting below 10 MHz. The photokinetics of one type of defect is compatible with ground-state electron-spin paramagnetism. The narrow and inhomogeneously broadened magnetic resonance spectrum differs significantly from the known spectra of in-plane defects. We determined a hyperfine coupling of ~10 MHz. Its angular dependence indicates an unpaired, out-of-plane delocalized π-orbital electron, probably originating from substitutional impurity atoms. We extracted spin-lattice relaxation times T of 13-17 μs with estimated spin coherence times T of less than 1 μs. Our results provide further insight into the structure, composition and dynamics of single optically active spin defects in hexagonal boron nitride.
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http://dx.doi.org/10.1038/s41563-021-00979-4DOI Listing
May 2021

AoiQ Catalyzes Geminal Dichlorination of 1,3-Diketone Natural Products.

J Am Chem Soc 2021 May 6. Epub 2021 May 6.

Leibniz Institute for Natural Product Research and Infection Biology - HKI, 07745 Jena, Germany.

Enzymes that can perform halogenation of aliphatic carbons are of significant interest to the synthetic and biocatalysis communities. Here we describe the characterization of AoiQ, a single-component flavin-dependent halogenase (FDH) that catalyzes dichlorination of 1,3-diketone substrates in the biosynthesis of dichlorodiaporthin. AoiQ represents the first biochemically reconstituted FDH that can halogenate an enolizable sp-hybridized carbon atom.
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http://dx.doi.org/10.1021/jacs.1c02868DOI Listing
May 2021

High-Performance Vertical Organic Transistors of Sub-5 nm Channel Length.

Nano Lett 2021 May 6. Epub 2021 May 6.

AG Physics of Nanosystems, Faculty of Physics, Ludwig-Maximilians-University, Munich, Munich 80799, Germany.

Miniaturization of electronic circuits increases their overall performance. So far, electronics based on organic semiconductors has not played an important role in the miniaturization race. Here, we show the fabrication of liquid electrolyte gated vertical organic field effect transistors with channel lengths down to 2.4 nm. These ultrashort channel lengths are enabled by using insulating hexagonal boron nitride with atomically precise thickness and flatness as a spacer separating the vertically aligned source and drain electrodes. The transistors reveal promising electrical characteristics with output current densities of up to 2.95 MA cm at -0.4 V bias, on-off ratios of up to 10, a steep subthreshold swing of down to 65 mV dec and a transconductance of up to 714 S m. Realizing channel lengths in the sub-5 nm regime and operation voltages down to 100 μV proves the potential of organic semiconductors for future highly integrated or low power electronics.
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http://dx.doi.org/10.1021/acs.nanolett.1c01144DOI Listing
May 2021

Odd Integer Quantum Hall States with Interlayer Coherence in Twisted Bilayer Graphene.

Nano Lett 2021 May 6. Epub 2021 May 6.

Max-Planck-Institut für Festköperforschung, 70569 Stuttgart, Germany.

We report on the quantum Hall effect in two stacked graphene layers rotated by 2°. The tunneling strength among the layers can be varied from very weak to strong via the mechanism of magnetic breakdown when tuning the density. Odd-integer quantum Hall physics is not anticipated in the regime of suppressed tunneling for balanced layer densities, yet it is observed. We interpret this as a signature of Coulomb interaction induced interlayer coherence and Bose-Einstein condensation of excitons that form at half filling of each layer. A density imbalance gives rise to reentrant behavior due to a phase transition from the interlayer coherent state to incompressible behavior caused by simultaneous condensation of both layers in different quantum Hall states. With increasing overall density, magnetic breakdown gains the upper hand. As a consequence of the enhanced interlayer tunneling, the interlayer coherent state and the phase transition vanish.
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http://dx.doi.org/10.1021/acs.nanolett.1c00360DOI Listing
May 2021

Rashba valleys and quantum Hall states in few-layer black arsenic.

Nature 2021 May 5;593(7857):56-60. Epub 2021 May 5.

Zhejiang Province Key Laboratory of Quantum Technology and Device, Department of Physics, Zhejiang University, Hangzhou, People's Republic of China.

Exciting phenomena may emerge in non-centrosymmetric two-dimensional electronic systems when spin-orbit coupling (SOC) interplays dynamically with Coulomb interactions, band topology and external modulating forces. Here we report synergetic effects between SOC and the Stark effect in centrosymmetric few-layer black arsenic, which manifest as particle-hole asymmetric Rashba valley formation and exotic quantum Hall states that are reversibly controlled by electrostatic gating. The unusual findings are rooted in the puckering square lattice of black arsenic, in which heavy 4p orbitals form a Brillouin zone-centred Γ valley with p symmetry, coexisting with doubly degenerate D valleys of p origin near the time-reversal-invariant momenta of the X points. When a perpendicular electric field breaks the structure inversion symmetry, strong Rashba SOC is activated for the p bands, which produces spin-valley-flavoured D valleys paired by time-reversal symmetry, whereas Rashba splitting of the Γ valley is constrained by the p symmetry. Intriguingly, the giant Stark effect shows the same p-orbital selectiveness, collectively shifting the valence band maximum of the D Rashba valleys to exceed the Γ Rashba top. Such an orchestrating effect allows us to realize gate-tunable Rashba valley manipulations for two-dimensional hole gases, hallmarked by unconventional even-to-odd transitions in quantum Hall states due to the formation of a flavour-dependent Landau level spectrum. For two-dimensional electron gases, the quantization of the Γ Rashba valley is characterized by peculiar density-dependent transitions in the band topology from trivial parabolic pockets to helical Dirac fermions.
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http://dx.doi.org/10.1038/s41586-021-03449-8DOI Listing
May 2021

Visualizing delocalized correlated electronic states in twisted double bilayer graphene.

Nat Commun 2021 May 4;12(1):2516. Epub 2021 May 4.

Department of Physics, University of California, Berkeley, CA, USA.

The discovery of interaction-driven insulating and superconducting phases in moiré van der Waals heterostructures has sparked considerable interest in understanding the novel correlated physics of these systems. While a significant number of studies have focused on twisted bilayer graphene, correlated insulating states and a superconductivity-like transition up to 12 K have been reported in recent transport measurements of twisted double bilayer graphene. Here we present a scanning tunneling microscopy and spectroscopy study of gate-tunable twisted double bilayer graphene devices. We observe splitting of the van Hove singularity peak by ~20 meV at half-filling of the conduction flat band, with a corresponding reduction of the local density of states at the Fermi level. By mapping the tunneling differential conductance we show that this correlated system exhibits energetically split states that are spatially delocalized throughout the different regions in the moiré unit cell, inconsistent with order originating solely from onsite Coulomb repulsion within strongly-localized orbitals. We have performed self-consistent Hartree-Fock calculations that suggest exchange-driven spontaneous symmetry breaking in the degenerate conduction flat band is the origin of the observed correlated state. Our results provide new insight into the nature of electron-electron interactions in twisted double bilayer graphene and related moiré systems.
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http://dx.doi.org/10.1038/s41467-021-22711-1DOI Listing
May 2021

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study.

J Gastroenterol 2021 May 3. Epub 2021 May 3.

Division of Gastroenterology, Department of Medicine, Iwate Medical University, Iwate, Japan.

Background: This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD).

Methods: Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn's disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn's Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC.

Results: A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426).

Conclusions: Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.
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http://dx.doi.org/10.1007/s00535-021-01793-0DOI Listing
May 2021

Gate-defined Josephson junctions in magic-angle twisted bilayer graphene.

Nat Nanotechnol 2021 May 3. Epub 2021 May 3.

Solid State Physics Laboratory, ETH Zurich, Zurich, Switzerland.

In situ electrostatic control of two-dimensional superconductivity is commonly limited due to large charge carrier densities, and gate-defined Josephson junctions are therefore rare. Magic-angle twisted bilayer graphene (MATBG) has recently emerged as a versatile platform that combines metallic, superconducting, magnetic and insulating phases in a single crystal. Although MATBG appears to be an ideal two-dimensional platform for gate-tunable superconductivity, progress towards practical implementations has been hindered by the need for well-defined gated regions. Here we use multilayer gate technology to create a device based on two distinct phases in adjustable regions of MATBG. We electrostatically define the superconducting and insulating regions of a Josephson junction and observe tunable d.c. and a.c. Josephson effects. The ability to tune the superconducting state within a single material circumvents interface and fabrication challenges, which are common in multimaterial nanostructures. This work is an initial step towards devices where gate-defined correlated states are connected in single-crystal nanostructures. We envision applications in superconducting electronics and quantum information technology.
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http://dx.doi.org/10.1038/s41565-021-00896-2DOI Listing
May 2021

Highly tunable junctions and non-local Josephson effect in magic-angle graphene tunnelling devices.

Nat Nanotechnol 2021 May 3. Epub 2021 May 3.

Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA.

Magic-angle twisted bilayer graphene (MATBG) has recently emerged as a highly tunable two-dimensional material platform exhibiting a wide range of phases, such as metal, insulator and superconductor states. Local electrostatic control over these phases may enable the creation of versatile quantum devices that were previously not achievable in other single-material platforms. Here we engineer Josephson junctions and tunnelling transistors in MATBG, solely defined by electrostatic gates. Our multi-gated device geometry offers independent control of the weak link, barriers and tunnelling electrodes. These purely two-dimensional MATBG Josephson junctions exhibit non-local electrodynamics in a magnetic field, in agreement with the Pearl theory for ultrathin superconductors. Utilizing the intrinsic bandgaps of MATBG, we also demonstrate monolithic edge tunnelling spectroscopy within the same MATBG devices and measure the energy spectrum of MATBG in the superconducting phase. Furthermore, by inducing a double-barrier geometry, the devices can be operated as a single-electron transistor, exhibiting Coulomb blockade. With versatile functionality encompassed within a single material, these MATBG tunnelling devices may find applications in graphene-based tunable superconducting qubits, on-chip superconducting circuits and electromagnetic sensing.
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http://dx.doi.org/10.1038/s41565-021-00894-4DOI Listing
May 2021

Experimental Determination of the Energy per Particle in Partially Filled Landau Levels.

Phys Rev Lett 2021 Apr;126(15):156802

Department of Physics, University of California, Santa Barbara, California 93106, USA.

We describe an experimental technique to measure the chemical potential μ in atomically thin layered materials with high sensitivity and in the static limit. We apply the technique to a high quality graphene monolayer to map out the evolution of μ with carrier density throughout the N=0 and N=1 Landau levels at high magnetic field. By integrating μ over filling factor ν, we obtain the ground state energy per particle, which can be directly compared to numerical calculations. In the N=0 Landau level, our data show exceptional agreement with numerical calculations over the whole Landau level without adjustable parameters as long as the screening of the Coulomb interaction by the filled Landau levels is accounted for. In the N=1 Landau level, a comparison between experimental and numerical data suggests the importance of valley anisotropic interactions and reveals a possible presence of valley-textured electron solids near odd filling.
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http://dx.doi.org/10.1103/PhysRevLett.126.156802DOI Listing
April 2021

Near-Field Excited Archimedean-like Tiling Patterns in Phonon-Polaritonic Crystals.

ACS Nano 2021 Apr 30. Epub 2021 Apr 30.

School of Chemical Engineering, University of New South Wales (UNSW), Sydney, NSW 2052, Australia.

Phonon-polaritons (PhPs) arise from the strong coupling of photons to optical phonons. They offer light confinement and harnessing below the diffraction limit for applications including sensing, imaging, superlensing, and photonics-based communications. However, structures consisting of both suspended and supported hyperbolic materials on periodic dielectric substrates are yet to be explored. Here we investigate phonon-polaritonic crystals (PPCs) that incorporate hyperbolic hexagonal boron nitride (hBN) to a silicon-based photonic crystal. By using the near-field excitation in scattering-type scanning near-field optical microscopy (s-SNOM), we resolved two types of repetitive local field distribution patterns resembling the Archimedean-like tiling on hBN-based PPCs, , dipolar-like field distributions and highly dispersive PhP interference patterns. We demonstrate the tunability of PPC band structures by varying the thickness of hyperbolic materials, supported by numerical simulations. Lastly, we conducted scattering-type nanoIR spectroscopy to confirm the interaction of hBN with photonic crystals. The introduced PPCs will provide the base for fabricating essential subdiffraction components of advanced optical systems in the mid-IR range.
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http://dx.doi.org/10.1021/acsnano.1c02507DOI Listing
April 2021

Resonant Tunneling Due to van der Waals Quantum-Well States of Few-Layer WSe in WSe/h-BN/p-MoS Junction.

Nano Lett 2021 May 26;21(9):3929-3934. Epub 2021 Apr 26.

Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505, Japan.

Few-layer transition metal dichalcogenides (TMDs) exhibit out-of-plane wave function confinement with subband quantization. This phenomenon is totally absent in monolayer crystals and is regarded as resulting from a naturally existing van der Waals quantum-well state. Because the energy separation between the subbands corresponds to the infrared wavelength range, few-layer TMDs are attractive for their potential to facilitate the application of TMD semiconductors as infrared photodetectors and emitters. Here, we report a few-layer WSe/h-BN tunnel barrier/multilayer p-MoS tunnel junction to access the quantized subbands of few-layer WSe via tunneling spectroscopy measurements. Resonant tunneling and a negative differential resistance were observed when the top of the valence band Γ-point of p-MoS was energetically aligned with one of the empty subbands at the Γ-point of few-layer WSe. These results demonstrate a critical step toward the utilization of subband quantization in few-layer TMD materials for infrared optoelectronics applications.
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http://dx.doi.org/10.1021/acs.nanolett.1c00555DOI Listing
May 2021

Accurate Measurement of the Gap of Graphene/h-BN Moiré Superlattice through Photocurrent Spectroscopy.

Phys Rev Lett 2021 Apr;126(14):146402

Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Monolayer graphene aligned with hexagonal boron nitride (h-BN) develops a gap at the charge neutrality point (CNP). This gap has previously been extensively studied by electrical transport through thermal activation measurements. Here, we report the determination of the gap size at the CNP of graphene/h-BN superlattice through photocurrent spectroscopy study. We demonstrate two distinct measurement approaches to extract the gap size. A maximum of ∼14  meV gap is observed for devices with a twist angle of less than 1°. This value is significantly smaller than that obtained from thermal activation measurements, yet larger than the theoretically predicted single-particle gap. Our results suggest that lattice relaxation and moderate electron-electron interaction effects may enhance the CNP gap in graphene/h-BN superlattice.
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http://dx.doi.org/10.1103/PhysRevLett.126.146402DOI Listing
April 2021

Josephson junction infrared single-photon detector.

Science 2021 04;372(6540):409-412

Raytheon BBN Technologies, Quantum Engineering and Computing Group Cambridge, MA 02138, USA.

Josephson junctions are superconducting devices used as high-sensitivity magnetometers and voltage amplifiers as well as the basis of high-performance cryogenic computers and superconducting quantum computers. Although device performance can be degraded by the generation of quasiparticles formed from broken Cooper pairs, this phenomenon also opens opportunities to sensitively detect electromagnetic radiation. We demonstrate single near-infrared photon detection by coupling photons to the localized surface plasmons of a graphene-based Josephson junction. Using the photon-induced switching statistics of the current-biased device, we reveal the critical role of quasiparticles generated by the absorbed photon in the detection mechanism. The photon sensitivity will enable a high-speed, low-power optical interconnect for future superconducting computing architectures.
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http://dx.doi.org/10.1126/science.abf5539DOI Listing
April 2021

Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial.

Lancet Gastroenterol Hepatol 2021 Apr 19. Epub 2021 Apr 19.

Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan. Electronic address:

Background: Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients with ulcerative colitis in remission. We therefore aimed to compare outcomes in these patients who continued infliximab with those who discontinued infliximab.

Methods: We did a multicentre, open-label randomised controlled trial at 24 specialist centres in Japan. We enrolled patients with ulcerative colitis who were in remission, had been treated with intravenous infliximab (5 mg/kg) every 8 weeks, and had started infliximab at least 14 weeks before study enrolment. No restrictions regarding age and comorbidities were used to exclude participation. Patients who were confirmed to be in remission for more than 6 months, to be corticosteroid-free, and to have a Mayo Endoscopic Subscore (MES) of 0 or 1 were centrally randomised. An independent organisation randomly assigned patients (1:1) into either the infliximab-continued group or infliximab-discontinued group, using a computer-generated stratified randomisation procedure. The stratified factors were the use of immunomodulators (yes or no) and MES (0 or 1). Neither patients nor health-care providers were masked to the randomisation. The primary endpoint was the remission rate at week 48 in the full analysis set, which was based on the intention-to-treat principle and excluded participants with no efficacy data after randomisation. This study was registered with the University Hospital Medical Information Network Center Trials registry, UMIN000012092.

Findings: Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80·4% [95% CI 66·1-90·6]) of 46 patients in the infliximab-continued group and 25 (54·3% [39·0-69·1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26·1% (95% CI 7·7-44·5; p=0·0076) before adjustment and 27·3% (95% CI 8·0-44·1; p=0·0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3·9% [95% CI -10·3 to 18·1]; p=0·59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66·7%, 95% CI 34·9-90·1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions.

Interpretation: Maintenance of remission was significantly more common in patients who continued infliximab than in those who discontinued. Discontinuing infliximab should therefore be discussed with caution, taking both risk of relapse and efficacy of re-treatment into account.

Funding: Mitsubishi Tanabe Pharma Corporation and the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan.

Translation: For the Japanese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2468-1253(21)00062-5DOI Listing
April 2021

The impact of cytochrome P450 3A genetic polymorphisms on tacrolimus pharmacokinetics in ulcerative colitis patients.

PLoS One 2021 22;16(4):e0250597. Epub 2021 Apr 22.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Tacrolimus (Tac) is an effective remission inducer of refractory ulcerative colitis (UC). Gene polymorphisms result in interindividual variability in Tac pharmacokinetics. In this study, we aimed to examine the relationships between gene polymorphisms and the metabolism, pharmacokinetics, and therapeutic effects of Tac in patients with UC. Forty-five patients with moderate-to-severe refractory UC treated with Tac were retrospectively enrolled. Genotyping for cytochrome P450 (CYP) 3A4*1G, CYP3A5*3, CYP2C19*2, CYP2C19*3, nuclear receptor subfamily 1 group I member 2 (NR1I2)-25385C>T, ATP-binding cassette subfamily C member 2 (ABCC2)-24C>T, ABCC2 1249G>A, and ABCC2 3972C>T was performed. Concentration/dose (C/D) ratio, clinical therapeutic effects, and adverse events were evaluated. The C/D ratio of Tac in UC patients with the CYP3A4*1G allele was statistically lower than in those with the CYP3A4*1/*1 allele (P = 0.005) and significantly lower in patients with CYP3A5*3/*3 than in those with CYP3A5*1 (P < 0.001). Among patients with the CYP3A4*1G allele, the C/D ratio was significantly lower in patients with CYP3A5*1 than in those with CYP3A5*3/*3 (P = 0.001). Patients with the NR1I2-25385C/C genotype presented significantly more overall adverse events than those with the C/T or T/T genotype (P = 0.03). Although CYP3A4*1G and CYP3A5*3 polymorphisms were related to Tac pharmacokinetics, CYP3A5 presented a stronger effect than CYP3A4. The NR1I2-25385C/C genotype was related to the overall adverse events. The evaluation of these polymorphisms could be useful in the treatment of UC with Tac.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250597PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062093PMC
April 2021

Evidence-based clinical practice guidelines for inflammatory bowel disease 2020.

J Gastroenterol 2021 Apr 22. Epub 2021 Apr 22.

Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease", The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.

Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn's disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.
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http://dx.doi.org/10.1007/s00535-021-01784-1DOI Listing
April 2021

Inter-Rater Reliability of Kampo Diagnosis for Chronic Diseases.

J Altern Complement Med 2021 Apr 16. Epub 2021 Apr 16.

Center for Kampo Medicine, Keio University School of Medicine, Tokyo, Japan.

This single-center observational study aimed to assess the inter-rater reliability (IRR) of Kampo medicine pattern diagnosis, which is modularized into three modules for chronic diseases, using 64 participants' information documents. The linearly weighted percentage of agreement and Gwet's agreement coefficient (AC) 2 for the deficiency-excess module, among three specialists, were 85.9% and 0.708, respectively. The unweighted percentage of agreement and Gwet's AC1 were 64.6% and 0.542 for the cold-heat, and 35.9% and 0.254 for the -blood-fluid modules, respectively. Our findings suggest that our modularization method may improve the IRR of Kampo medicine pattern diagnosis.
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http://dx.doi.org/10.1089/acm.2020.0298DOI Listing
April 2021

Strain fields in twisted bilayer graphene.

Nat Mater 2021 Apr 15. Epub 2021 Apr 15.

Department of Chemistry, University of California, Berkeley, CA, USA.

Van der Waals heteroepitaxy allows deterministic control over lattice mismatch or azimuthal orientation between atomic layers to produce long-wavelength superlattices. The resulting electronic phases depend critically on the superlattice periodicity and localized structural deformations that introduce disorder and strain. In this study we used Bragg interferometry to capture atomic displacement fields in twisted bilayer graphene with twist angles <2°. Nanoscale spatial fluctuations in twist angle and uniaxial heterostrain were statistically evaluated, revealing the prevalence of short-range disorder in moiré heterostructures. By quantitatively mapping strain tensor fields, we uncovered two regimes of structural relaxation and disentangled the electronic contributions of constituent rotation modes. Further, we found that applied heterostrain accumulates anisotropically in saddle-point regions, generating distinctive striped strain phases. Our results establish the reconstruction mechanics underpinning the twist-angle-dependent electronic behaviour of twisted bilayer graphene and provide a framework for directly visualizing structural relaxation, disorder and strain in moiré materials.
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http://dx.doi.org/10.1038/s41563-021-00973-wDOI Listing
April 2021

Nematicity and competing orders in superconducting magic-angle graphene.

Science 2021 04;372(6539):264-271

Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Strongly interacting electrons in solid-state systems often display multiple broken symmetries in the ground state. The interplay between different order parameters can give rise to a rich phase diagram. We report on the identification of intertwined phases with broken rotational symmetry in magic-angle twisted bilayer graphene (TBG). Using transverse resistance measurements, we find a strongly anisotropic phase located in a "wedge" above the underdoped region of the superconducting dome. Upon its crossing with the superconducting dome, a reduction of the critical temperature is observed. Furthermore, the superconducting state exhibits an anisotropic response to a direction-dependent in-plane magnetic field, revealing nematic ordering across the entire superconducting dome. These results indicate that nematic fluctuations might play an important role in the low-temperature phases of magic-angle TBG.
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http://dx.doi.org/10.1126/science.abc2836DOI Listing
April 2021

Bias-controlled multi-functional transport properties of InSe/BP van der Waals heterostructures.

Sci Rep 2021 Apr 12;11(1):7843. Epub 2021 Apr 12.

School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea.

Van der Waals (vdW) heterostructures, consisting of a variety of low-dimensional materials, have great potential use in the design of a wide range of functional devices thanks to their atomically thin body and strong electrostatic tunability. Here, we demonstrate multi-functional indium selenide (InSe)/black phosphorous (BP) heterostructures encapsulated by hexagonal boron nitride. At a positive drain bias (V), applied on the BP while the InSe is grounded, our heterostructures show an intermediate gate voltage (V) regime where the current hardly changes, working as a ternary transistor. By contrast, at a negative V, the device shows strong negative differential transconductance characteristics; the peak current increases up to ~5 μA and the peak-to-valley current ratio reaches 1600 at V = -2 V. Four-terminal measurements were performed on each layer, allowing us to separate the contributions of contact resistances and channel resistance. Moreover, multiple devices with different device structures and contacts were investigated, providing insight into the operation principle and performance optimization. We systematically investigated the influence of contact resistances, heterojunction resistance, channel resistance, and the thickness of BP on the detailed operational characteristics at different V and V regimes.
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http://dx.doi.org/10.1038/s41598-021-87442-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041794PMC
April 2021

High mobility field-effect transistors based on MoS2 crystal grown by the flux method.

Nanotechnology 2021 Apr 12. Epub 2021 Apr 12.

School of Electronic and Electrical Engineering, Sungkyunkwan University, 300 Chun chun dong, Jangan - gu, Suwon-city 440-746, KOREA, Suwon, Korea (the Republic of).

Two-dimensional (2D) molybdenum disulphide (MoS2) transition metal chalcogenides (TMDs) have great potential in optical and electronic device applications; however, the performance of MoS2 is limited by its crystal quality, which serves as a measure of defects and grain boundaries in the grown material. Therefore, high-quality growth of MoS2 crystals continues to be a critical issue. In this context, we propose the formation of high-quality MoS2 crystals via flux method. The electrical properties demonstrate the significant impact of crystal morphology on the performance of the MoS2 field-effect transistor. MoS2 material with relatively higher concentration of sulphur (molar ratio of 2.2) and cooling temperature rate of 2.5 °C/h yielded good quality and optimally sized crystals. The room temperature and low temperature (77 K) electrical transport properties of MoS2 field-effect transistors (FETs) were studied in detail with and without h-BN dielectric to cope up with the mobility degradation issue due to scattering at SiO2/2D material interface. The highest field-effect mobility of 113 cm2V-1s-1 was achieved at 77 K for the MoS2/h-BN FET following high-quality crystal formation by flux method. Our result notifies the achievement of large-scale high-quality crystal growth with reduced defect density using the flux method and is the key to achieving higher mobility in MoS2 FET devices in parallel to commercially accessible MoS2 crystals.
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http://dx.doi.org/10.1088/1361-6528/abf6f1DOI Listing
April 2021

Correction to: Discovery and investigation of natural Diels-Alderases.

Authors:
Kenji Watanabe

J Nat Med 2021 Apr 8. Epub 2021 Apr 8.

Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.

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http://dx.doi.org/10.1007/s11418-021-01511-3DOI Listing
April 2021

Isospin Pomeranchuk effect in twisted bilayer graphene.

Nature 2021 Apr 7;592(7853):220-224. Epub 2021 Apr 7.

Department of Physics, University of California at Santa Barbara, Santa Barbara, CA, USA.

In condensed-matter systems, higher temperatures typically disfavour ordered phases, leading to an upper critical temperature for magnetism, superconductivity and other phenomena. An exception is the Pomeranchuk effect in He, in which the liquid ground state freezes upon increasing the temperature, owing to the large entropy of the paramagnetic solid phase. Here we show that a similar mechanism describes the finite-temperature dynamics of spin and valley isospins in magic-angle twisted bilayer graphene. Notably, a resistivity peak appears at high temperatures near a superlattice filling factor of -1, despite no signs of a commensurate correlated phase appearing in the low-temperature limit. Tilted-field magnetotransport and thermodynamic measurements of the in-plane magnetic moment show that the resistivity peak is connected to a finite-field magnetic phase transition at which the system develops finite isospin polarization. These data are suggestive of a Pomeranchuk-type mechanism, in which the entropy of disordered isospin moments in the ferromagnetic phase stabilizes the phase relative to an isospin-unpolarized Fermi liquid phase at higher temperatures. We find the entropy, in units of Boltzmann's constant, to be of the order of unity per unit cell area, with a measurable fraction that is suppressed by an in-plane magnetic field consistent with a contribution from disordered spins. In contrast to He, however, no discontinuities are observed in the thermodynamic quantities across this transition. Our findings imply a small isospin stiffness, with implications for the nature of finite-temperature electron transport, as well as for the mechanisms underlying isospin ordering and superconductivity in twisted bilayer graphene and related systems.
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http://dx.doi.org/10.1038/s41586-021-03409-2DOI Listing
April 2021

Entropic evidence for a Pomeranchuk effect in magic-angle graphene.

Nature 2021 Apr 7;592(7853):214-219. Epub 2021 Apr 7.

Department of Condensed Matter Physics, Weizmann Institute of Science, Rehovot, Israel.

In the 1950s, Pomeranchuk predicted that, counterintuitively, liquid He may solidify on heating. This effect arises owing to high excess nuclear spin entropy in the solid phase, where the atoms are spatially localized. Here we find that an analogous effect occurs in magic-angle twisted bilayer graphene. Using both local and global electronic entropy measurements, we show that near a filling of one electron per moiré unit cell, there is a marked increase in the electronic entropy to about 1k per unit cell (k is the Boltzmann constant). This large excess entropy is quenched by an in-plane magnetic field, pointing to its magnetic origin. A sharp drop in the compressibility as a function of the electron density, associated with a reset of the Fermi level back to the vicinity of the Dirac point, marks a clear boundary between two phases. We map this jump as a function of electron density, temperature and magnetic field. This reveals a phase diagram that is consistent with a Pomeranchuk-like temperature- and field-driven transition from a low-entropy electronic liquid to a high-entropy correlated state with nearly free magnetic moments. The correlated state features an unusual combination of seemingly contradictory properties, some associated with itinerant electrons-such as the absence of a thermodynamic gap, metallicity and a Dirac-like compressibility-and others associated with localized moments, such as a large entropy and its disappearance under a magnetic field. Moreover, the energy scales characterizing these two sets of properties are very different: whereas the compressibility jump has an onset at a temperature of about 30 kelvin, the bandwidth of magnetic excitations is about 3 kelvin or smaller. The hybrid nature of the present correlated state and the large separation of energy scales have implications for the thermodynamic and transport properties of the correlated states in twisted bilayer graphene.
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http://dx.doi.org/10.1038/s41586-021-03319-3DOI Listing
April 2021